Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost
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Abstract
The emergence of SARS-CoV-2 Variants of Concern (VOCs) with mutations in key neutralizing antibody epitopes threatens to undermine vaccines developed against the pandemic founder variant (Wu-Hu-1). Widespread vaccine rollout and continued transmission are creating a population that has antibody responses of varying potency to Wu-Hu-1. Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet known whether heterotypic vaccine boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the primed memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. Here, we show that a single adjuvanted dose of receptor binding domain (RBD) protein from VOC 501Y.V2 (B.1.351) drives an extremely potent neutralizing antibody response capable of cross-neutralizing both Wu-Hu-1 and 501Y.V2 in rhesus macaques previously immunized with Wu-Hu-1 spike protein. Passive immunization with plasma sampled following this boost protected K18-hACE2 mice from lethal challenge with a 501Y.V2 clinical isolate, whereas only partial protection was afforded by plasma sampled after two Wu-Hu-1 spike immunizations.
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SciScore for 10.1101/2021.04.03.438330: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics statement: The animal work was conducted with the approval of the regional Ethical Committee on Animal Experiments (Stockholms Norra Djurförsöksetiska Nämnd). Randomization Using a Generalized Linear Model, we model the daily variant counts with a multinomial distribution (and a log-link function), with underlying frequencies parameterized by a linear combination of 400 randomly drawn Fourier basis features (aka. a “Random Kitchen Sink” 22) to allow frequencies to vary non-linearly as a function of time. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
… SciScore for 10.1101/2021.04.03.438330: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Ethics statement: The animal work was conducted with the approval of the regional Ethical Committee on Animal Experiments (Stockholms Norra Djurförsöksetiska Nämnd). Randomization Using a Generalized Linear Model, we model the daily variant counts with a multinomial distribution (and a log-link function), with underlying frequencies parameterized by a linear combination of 400 randomly drawn Fourier basis features (aka. a “Random Kitchen Sink” 22) to allow frequencies to vary non-linearly as a function of time. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Pseudotyped neutralization assays: HEK293T and HEK293T-hACE2 (human:female) cells were cultured in a humidified 37°C incubator (5% CO2) in Dulbecco’s Modified Eagle Medium (Gibco) supplemented with 10% Fetal Bovine Serum and 1% Penicillin/Streptomycin, and were passaged when nearing confluency using 1X Trypsin-EDTA. HEK293Tsuggested: NonePseudotyped viruses sufficient to generate 50,000 relative light units (RLUs) were incubated with serial dilutions of plasma for 60 min at 37°C in a 96-well plate, and then 15,000 HEK293T-hACE2 cells were added to each well. HEK293T-hACE2suggested: NoneSoftware and Algorithms Sentences Resources ID50 titers were interpolated as the reciprocal plasma dilution where RLUs were reduced by 50% relative to control wells in the absence of serum, fitting a four-parameter logistic curve in Prism 9 (GraphPad Software). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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